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Biomedical subjects

P A Henricks

Publications and source records attributed to P A Henricks.

At least 19 recordsLinked to original sources
PubMed1996

LFA-1, and not Mac-1, is crucial for the development of hyperreactivity in a murine model of nonallergic asthma.

In this study, we investigated the importance of the beta 2-integrins for the development of tracheal hyperreactivity in a murine model for nonallergic asthma. The response was induced by skin sensitization with dinitrofluorobenzene (DNFB) followed by an intranasal challenge with the same hapten. Twenty-four hours after the challenge, tracheal hyperreactivity, a decrease in T cells in the blood, and increased neutrophil numbers in bronchoalveolar lavage fluid (BALF) and blood were observed. Monoclonal antibodies (mAbs) directed against the alpha-chains of LFA-1 (FD441.8) and Mac-1 (M1/70) were injected intravenously 2 h before and 2 h after the challenge. Treatment with anti-LFA-1 mAb totally inhibited the development of tracheal hyperreactivity measured 24 h after the challenge, whereas anti-Mac-1 mAb had only a partial effect on this response. The decrease in T cells in the blood, which was also evident 24 h after the challenge, was totally inhibited by treatment with anti-LFA-1, whereas anti-Mac-1 had little effect. The increase in the number of neutrophils in BALF at this time point was completely inhibited by both anti-LFA-1 and anti-Mac-1. In summary, evidence presented in this report highlights the possible importance of the adhesion molecule LFA-1 in the development of tracheal hyperreactivity. Our results suggest that LFA-1 present on T cells may play an integral role in this response.

Animals↗
PubMed1995

The linoleic acid metabolite 13-HODE modulates degranulation of human polymorphonuclear leukocytes.

The effect of the linoleic acid metabolite 13-hydroxyoctadecadienoic acid human polymorphonuclear leukocytes (PMNs) was investigated by measuring the expression of CD11b and CD67 on the plasma membrane. 13-HODE (5 microM) by itself induced degranulation of PMNs, but to a lesser extent as compared to PAF and fMLP. In addition, 13-HODE was found to inhibit the PAF-induced degranulation whereas an additive effect on the fMLP-induced PMNs degranulation was observed. These results indicate that 13-HODE can play a modulatory role in degranulation of PMNs.

Antigens, CD↗
PubMed1995

Adhesion molecules: a new target for immunoliposome-mediated drug delivery.

The anti-ICAM-1 monoclonal antibody F10.2 was conjugated to liposomes to target to cells expressing the cell adhesion molecule ICAM-1. We demonstrate that F10.2 immunoliposomes bind to human bronchial epithelial cells (BEAS-2B) and human umbilical vein endothelial cells (HUVEC) in a specific, dose- and time-dependent manner. It appears that the degree of ICAM-1 expression is the limiting factor in the degree of immunoliposome binding to the cells. These results are a first step in the strategy for specific drug delivery to target sites characterised by increased expression of adhesion molecules.

Antibodies, Monoclonal↗
PubMed1995

Preparation of bovine tracheal smooth muscle for in vitro pharmacological studies.

In this study a new method is described for standardization of both length and weight of bovine tracheal smooth muscle strips to be used for measuring airway responsiveness in vitro. Tracheal smooth muscle was cut into strips 2.5-mm thick and 10-mm long with an average wet weight of 25.9 +/- 0.6 mg (n = 5). By use of preloads varying from 0.5 to 10 g, it was found that 5 g caused the highest contraction and relaxation of the tissues in response to pharmacological agents. Moreover, at a preload of 5 g the variations among the maximal responses induced by histamine, methacholine, KCl, and salbutamol were very small (standard errors being 6.8%, 5.0%, 2.5%, and 1.6% of the corresponding average maximal response) as well as were the variations in the pD2 values.

Airway Resistance↗
PubMed1995

13-Hydroxy-linoleic acid induces airway hyperresponsiveness to histamine and methacholine in guinea pigs in vivo.

The influence of 13-hydroxy-linoleic acid (13-HODE) on the pulmonary resistance and dynamic compliance of guinea pigs in vivo was determined. Intravenously administered histamine and methacholine caused dose-dependent increases in pulmonary resistance and dose-dependent decreases in dynamic compliance in anesthetized, spontaneously breathing guinea pigs. Inhalation of an aerosol containing 13-HODE (10 mumol/L) enhanced the increases in pulmonary resistance observed after administration of histamine or methacholine when compared with the respective control animals. The effect of 13-HODE on the increase in pulmonary resistance after administration of histamine was dose-dependent. An enhancement in the pulmonary resistance was already measured after treatment of guinea pigs with aerosols of solutions containing 0.1 mumol/L 13-HODE when compared with that of control animals. In contrast, the changes in dynamic compliance were not affected by 13-HODE. These results indicate that 13-HODE may play an important role in the induction of airway hyperresponsiveness in vivo when it is produced or released in significant amounts in the airways.

Airway Resistance↗
PubMed1995

Hypotensive effect of 13-hydroxylinoleic acid in the rat: mediation via the release of a CGRP-like mediator from capsaicin-sensitive nerves.

1. The effect of 13-hydroxylinoleic acid (13-HODE) on changes in blood pressure in the rat was measured. 2. 13-HODE (0.1 - 100 micrograms kg-1) had no direct effect on blood pressure in the rat and had no effect on histamine (0.1 - 1000 micrograms kg-1)-induced changes in blood pressure. In contrast, it was found that 13-HODE itself induced a decrease in diastolic arterial blood pressure when it was injected intravenously after either a single dose of histamine (10, 100 or 1000 micrograms kg-1) or after a dose-response curve of histamine (0.1 - 1000 micrograms kg-1). 3. This hypotensive effect of 13-HODE was not observed after administration of the endothelium-dependent vasodilator, acetylcholine (0.1 - 10 micrograms kg-1), the endothelium-independent vasodilator, sodium nitroprusside (0.1 - 100 micrograms kg-1) or the inflammatory mediator, leukotriene B4 (0.1 - 300 micrograms kg-1). However, prior injection of bradykinin (0.1 - 100 micrograms kg-1) allowed a dose-dependent hypotensive effect of 13-HODE to be revealed. 4. The hypotensive effect of 13-HODE after histamine and bradykinin could be inhibited by neonatal capsaicin treatment of the rats (50 mg kg-1, s.c. on day 1 and 2 after birth). 5. Ruthenium red (120 micrograms kg-1 min-1), an inhibitor of excitatory effects on sensory nerves, and the CGRP antagonist, CGRP8-37 (1-3 micrograms kg-1 min-1) also inhibited the hypotensive effect of 13-HODE. 6. It is concluded that the hypotensive effect of 13-HODE in the rat after histamine and bradykinin is due to the release of a CGRP-like substance from sensory nerves. These results highlight the possibility that endogenous 13-HODE could be involved in the neurogenic regulation of blood pressure.

Acetylcholine↗
PubMed1995

Effect of methacholine on mucociliary transport in bovine trachea in vitro.

A method is described to evaluate pharmacologic influence on bovine tracheal mucus transport in vitro. In this model, cholinergic agonist methacholine stimulated transport velocity. Methacholine at concentration of 10(-6)M increased velocity by 13.6%, whereas 10(-5)M increased velocity by 26%. Stimulation was inhibited by atropine.

Analysis of Variance↗
PubMed1994

13-HODE inhibits the intracellular calcium increase of activated human polymorphonuclear cells.

We studied the effect of the linoleic acid metabolite 13-hydroxyoctadecadienoic acid (13-HODE) on the increase of the intracellular calcium concentration, [Ca2+]i, induced by platelet-activating factor (PAF), leukotriene B4 (LTB4), and formyl-Met-Leu-Phe (fMLP) in human polymorphonuclear leukocytes (PMNs). 13-HODE by itself did not change the [Ca2+]i of PMNs. However, when PMNs were preincubated with 13-HODE and subsequently stimulated with PAF, LTB4, or fMLP, an inhibition of the increase of the [Ca2+]i was observed. The PAF-induced calcium response was concentration-dependently inhibited between 0.1 and 5 microM 13-HODE. These results suggest that 13-HODE can affect the increase of the [Ca2+]i and hence can modulate activation of PMNs.

Amino Acid Sequence↗
PubMed1994

Effect of climatic stress on the immunological reactivity of weaned pigs.

Weaned pigs exposed daily to either unpredictable draught (experiment 1) or intermittent unpredictable draught (experiment 2) showed different lymphocyte blastogenic responses after mitogenic stimulation with phytohaemagglutinin (PHA) and concanavalin A (ConA). In both experiments PHA skin test responses were lower for draught exposed pigs than for control pigs and leucocyte numbers or profiles were altered compared to those of control pigs. Superoxide production and chemiluminescence of porcine granulocytes were similar for draught exposed and control animals. Furthermore, serum globulin content did not differ significantly between pigs in the experimental and control room. The strong increase in serum gamma-globulin after the Aujeszky Disease Virus (ADV)-challenge was the same for draught exposed and control pigs. The same held for the lymphocyte blastogenic response with ADV protein as antigenic stimulus. The present study shows the effects of climatic stress on immunological reactivity, which may reflect a homeostatic disturbance of the pig's immune system elicited by exposure to unpredictable draught.

Animals↗
PubMed1993

Effects of parainfluenza type 3 virus on guinea pig pulmonary alveolar macrophage functions in vitro.

The influence of parainfluenza type 3 (PI-3) virus on the release of inflammatory mediators by guinea pig pulmonary alveolar macrophages (PAMs) was investigated in vitro. Direct application of PI-3 virus dose-dependently stimulated the generation of chemiluminescence by PAMs and induced aggregation of PAMs. No significant effects of PI-3 virus on the release of linoleic acid metabolites by PAMs were detected. However, an increased release of the arachidonic acid metabolite thromboxane B2 (TxB2) was observed when PAMs were stimulated with PI-3 virus. PAMs were also cultured for 2 h or 18 h in the presence of PI-3 virus or control medium. The production of reactive oxygen species and the release of fatty acid metabolites by these PAMs were determined upon stimulation with opsonized zymosan particles or phorbol myristate acetate. The amounts of hydrogen peroxide and superoxide produced did not differ between virus- and control medium-incubated PAMs. However, the PI-3 virus-treated PAMs generated twice as much chemiluminescence when compared to PAMs incubated with control medium. The 2-h incubation period with PI-3 virus also resulted in a decreased release of TxB2 from the PAMs upon zymosan stimulation. The changes in the production of reactive oxygen species and the release of TxB2 by PAMs could account for damage to the airways and bronchial hyperresponsiveness often seen after viral infection.

Animals↗
PubMed1993

Expression and modulation of adhesion molecules on human bronchial epithelial cells.

Epithelial damage in the airways is a feature often observed in patients with asthma and is probably caused by the interaction of epithelial cells with leukocytes. As adhesion molecules are thought to be important in this interaction, we analyzed the expression and modulation of adhesion molecules on primary cultured human bronchial epithelial cells and the bronchial epithelial cell lines BEAS-2B and NCI-H292. E-selectin, P-selectin, and VCAM-1 were absent under basal and stimulated conditions. The adhesion molecules ICAM-1 (CD54), LFA-3 (CD58), and CD44 (H-CAM) were expressed basally on primary cultured human bronchial epithelial cells and the BEAS-2B and NCI-H292 cell lines. CD44 and LFA-3 expression did not change after stimulation with IFN-gamma or TNF-alpha. In contrast, ICAM-1 expression on human bronchial epithelial cells and BEAS-2B cells could be increased by incubation with PMA, IFN-gamma, TNF-alpha, and especially with the combination of IFN-gamma and TNF-alpha. The maximal ICAM-1 expression on both epithelial cell types was obtained with the combination of TNF-alpha and IFN-gamma after 48 h of incubation. The NCI-H292 cell line was different in that it only showed increased ICAM-1 expression after stimulation with PMA and IFN-gamma and not by the combination of IFN-gamma and TNF-alpha or with TNF-alpha alone. In conclusion, the bronchial epithelial cells tested express several adhesion molecules, but only ICAM-1 expression was influenced by inflammatory cytokines.

Bronchi↗
PubMed1993

Preinfection chemotactic response of blood polymorphonuclear leukocytes to predict severity of Escherichia coli mastitis.

Experimental mastitis was induced by inoculating rear right quarters of 10 healthy cows with 10(3) cfu of Escherichia coli. The chemotactic responses of peripheral blood polymorphonuclear leukocytes at d-6, -5, -2, -1, and immediately prior to inoculation were measured. Chemiluminescence of polymorphonuclear leukocytes was measured immediately prior to inoculation. Severity of the experimental mastitis was assessed by bacterial growth in the inoculated quarters. Results of this study indicated that severity of the experimental mastitis may be predicted by the chemotactic response in vitro of polymorphonuclear leukocytes isolated from the peripheral blood at d 2, d 1, and immediately prior to inoculation. The number of circulating polymorphonuclear leukocytes immediately prior to inoculation also showed a negative relationship with the severity of mastitis. No relationship existed between preinfection chemiluminescence of polymorphonuclear leukocytes and the severity of the experimental mastitis.

Animals↗
PubMed1992

13-hydroxyoctadecadienoic acid attenuates oedema formation induced by leukotriene B4 in vivo in rabbit skin.

Intradermal 13-hydroxyoctadecadienoic acid (13-HODE; 10(-11)-10(-9) mol/site) inhibited oedema formation induced by the neutrophil-dependent mediator leukotriene B4 (LTB4) in the presence of calcitonin gene-related peptide (CGRP; 10(-11) mol/site) in rabbit skin. In contrast, the responses to the direct acting mediators bradykinin and histamine were unaffected by 13-HODE. 13-HODE failed to induce oedema formation in rabbit skin when injected alone or in the presence of the potent vasodilator CGRP. These results present a novel interaction between 13-HODE and LTB4 that could have important implications in the pathogenesis of inflammation.

Analysis of Variance↗
PubMed1992

A procedure for parallel isolation of white blood cells, granulocyte and purified neutrophil suspensions from the peripheral blood of cattle.

A rapid method is described for parallel isolation of white blood cells, granulocytes and purified neutrophils from peripheral blood of normal cattle. The mean recovery (+/- S.D.) of white blood cells, granulocytes and purified neutrophils isolated from peripheral blood of 13 cows was 66.4 +/- 12.6%, 68.7 +/- 20.0% and 38.0 +/- 20.9%, respectively. The mean purity of the isolated granulocyte and neutrophil suspensions was 94.0 +/- 3.8% and 95.0 +/- 6.0%, respectively. Viability of isolated cells was more than 97%.

Animals↗
PubMed1992

Pasteurella haemolytica leukotoxin enhances production of leukotriene B4 and 5-hydroxyeicosatetraenoic acid by bovine polymorphonuclear leukocytes.

The influence of the leukotoxin of Pasteurella haemolytica on the generation of arachidonic acid metabolites by bovine polymorphonuclear leukocytes (PMNs) was investigated. PMNs released 5-, 12-, and 15-hydroxyeicosatetraenoic acids (5-, 12-, and 15-HETE) and leukotriene B4 (LTB4) upon stimulation with arachidonic acid. The leukotoxin preparations dose dependently enhanced the release of the 5-lipoxygenase products 5-HETE and LTB4 in arachidonic acid-stimulated PMNs, whereas the release of 12- and 15-HETE was not affected. The enhanced release of LTB4 and 5-HETE was not due to a decreased cellular retention of the 5-lipoxygenase products. In addition, leukotoxin preparations by themselves were also able to induce LTB4 and 5-HETE production in the absence of exogenous arachidonic acid. Generation of 5-lipoxygenase products by PMNs stimulated by leukotoxin may represent an important cellular event that occurs during infections with P. haemolytica.

Animals↗